IMMUNODEFICIENCY VIRUS TYPE-1 QUANTITATIVE CELL MICROCULTURE AS A MEASURE OF ANTIVIRAL EFFICACY IN A MULTICENTER CLINICAL

A quantitative cell microculture assay (QMC) was used to measure the h uman immunodeficiency virus type 1 (HIV-1) peripheral blood mononuclea r cell (PBMC)-associated titer in 109 subjects enrolled in an open-lab el phase I/II study of didanosine monotherapy or combination therapy w ith zidovudine. The titer was inversely correlated with CD4(+) cell co unt at baseline (r = .37, P = .001). After 12 weeks of therapy, subjec ts showed a significant decreases in virus titer and those with the hi ghest baseline virus titers had the greatest increase in CD4(+) cell n umber (r = .430, P = .002). The QMC assay was more sensitive (98%) for assessing the antiretroviral effect of therapy than was immune comple x-dissociated HIV p24 antigen (32%) or plasma culture (3.4%). Estimate d sample sizes for phase I/II clinical trials were derived using the w ithin-subject QMC SD of .72 log(10) infectious units per 10(6) PMBC.